Estudo de associação dos genes do inflamassoma na COVID-19

Abstract

COVID-19, caused by the SARS-CoV-2 coronavirus, exhibits considerable clinical heterogeneity, with manifestations ranging from asymptomatic infections to severe respiratory syndromes, which are among the leading causes of severe complications and death related to the disease. Disease severity is strongly associated with dysregulation of the immune response, particularly the hypersecretion of pro-inflammatory cytokines such as IL-1β and IL-18. In this context, the NLRP3 inflammasome, activated during viral infection, plays a central role by inducing the release of these cytokines, promoting exacerbated inflammation and contributing to disease progression to more severe forms. The observed difference in the intensity of the inflammatory response among individuals suggests a potential genetic contribution. Single nucleotide variants (SNVs) have been identified as genetic alterations capable of influencing gene expression or function, potentially enhancing or disrupting biological mechanisms. However, data on the functional impact of these variants remain limited, especially in genetically diverse populations such as the Brazilian population. This study evaluated the association between SNVs in genes related to the inflammasome and COVID-19 severity through a case-control study involving 800 adults infected with SARS-CoV-2, equally distributed between mild/moderate and severe/critical cases. Genotyping was performed using qPCR for SNVs in the NLRP3 (rs7525979, rs35829419, rs10754558), CASP1 (rs572687), and IL1B (rs1143634, rs1143629) genes. No statistically significant associations were found between variants in the IL1B and CASP1 genes and disease severity. In contrast, gain-of-function variants in NLRP3 (rs35829419 and rs10754558) showed a significant association with a protective effect against progression to severe forms and mortality due to COVID-19 (p < 0.05). These findings reinforce the role of the NLRP3 inflammasome in the pathophysiology of the disease and suggest the potential of these variants as prognostic biomarkers of severity.